3.A.1.210.12ABCB3 of 704 aas and 6 TMSs. Essential for the biosynthesis of heme in mitochondria, and of iron-sulfur centers (ISC) in the cytoplasm. The protein is an ABC half-transporter that has an N-terminal extension required to target LmABCB3 to the
mitochondrion. Martínez-García et al. 2016 showed that LmABCB3 interacts with porphyrins and is required for the
mitochondrial synthesis of heme from a host precursor. It complements the severe growth defect in yeast
lacking ATM1, an orthologue of human ABCB7, involved in exporting from mitochondria a gluthatione-containing compound required for the
generation of cytosolic ISC. Docking analyzes using trypanothione, the main thiol in the
parasite, showed how both, LmABCB3 and yeast ATM1, contain a
similar thiol-binding pocket. LmABCB3 is an essential gene as dominant negative
inhibition of LmABCB3 is lethal for the parasite. The
abrogation of only one allele of the gene did not impede promastigote
growth in axenic culture but prevented the replication of intracellular
amastigotes and the virulence of the parasites in a mouse model of
cutaneous leishmaniasis.